HIF-2α、ABCG2、OCT-4与胃癌化疗耐药的关系研究

Correlation of HIF-2α, ABCG2 and OCT-4 with chemotherapy resistance in human gastric cancer

目的探讨HIF-2α、ABCG2、OCT-4与人胃癌化疗耐药的关系。方法 2011年1月-2013年6月在我院消化科就诊的符合条件的经电子胃镜和病理证实为晚期胃癌的患者52例,均采用FOL-FOX4全身化疗,根据化疗效果的不同分为有效[包括完全缓解(CR)和部分缓解(PR)]组、稳定(SD)组、进展(PD)组。采用RT-PCR、免疫组织化学染色检测不同治疗效果肿瘤组织中HIF-2α、ABCG2、OCT-4 m RNA及蛋白的表达。结果 52例患者经过4周期FOL-FOX4方案化疗,其中CR 2例,PR 19例,SD 25例,PD 6例。即有效(CR+PR)组21例(40.4%),稳定组25例(48.1%),进展组6例(11.5%)。CR+PR组中HIF-2α、ABCG2、OCT-4 m RNA及蛋白呈低水平表达,SD组HIF-2α、ABCG2、OCT-4 m RNA及蛋白的表达较CR+PR组明显增加,PD组表达进一步增加,CR+PR组、SD组和PD两两比较,差异均有统计学意义(P<0.05)。结论 HIF-2α、ABCG2、OCT-4等肿瘤干细胞标记物的m RNA和蛋白在肿瘤组织中的表达水平与肿瘤的化疗效果有关,其高水平表达或许是化疗效果差和耐药的主要原因之一。

Objective To investigate the correlation of HIF-2ot, ABCG2 and OCT-4 with chemotherapy resistant gastric cancer in humans. Methods Fifty-two patients who were confirmed to have advanced gastric cancer with the aid of electronic endoscopy and pathology in the Department of Gastroenterology, Affiliated Hospital of Weifang Medical College, were enrolled in the study. According to the effect of FOL-FOX4 chemotherapy that these patients had experienced, they were divided into three groups： CR＋PR （complete remission＋partial remission） group, SD （stable disease） group and PD （progressive disease） group. The expression levels of HIF-2α, ABCG2, and OCT-4 mRNA and protein were assessed in different groups by using RT-PCR and immunocytochemistry. Results Two patients achieved CR, 19 achieved PR, 25 showed SD, and 6 showed PD. In other words, CR＋PR were seen in 21 patients （40.4%）, SD in 25（48.1%）, PD in 6（11.5%）. In CR＋PR group, the expression levels of HIF-2α, ABCG2 and OCT4 mRNA and protein were low, but the above mentioned expressions were significantly increased in SD group and PD group. The expression levels of HIF-2α, ABCGZ and Oct-4 mRNA and protein were highest in the PD group, lower in the SD group, and lowest in the CR ＋ PR groups （all P〈0.0S）. Conclusions The expression of the markers HIF-2α, ABCG2 and OCT4 in human tumor tissues is related to the effect of chemotherapy for gastric cancer. A high expression of tumor markers is perhaps the main reason for low efficacy of chemotherapy due to drug resistance.